MSGM Clinical Case Discussion August 2026

The Valproate Trap: When Parkinson’s" and Dementia Are Found in a

Pillbox

Prepared by Dr. Khaw Mae Jane

Supervised by Dato' Dr. Tunku Muzafar Shah, Dr. Chee Sing Hui

Case Summary

Patient Profile & Background

Mdm PCL is a 64-year-old Chinese lady (Clinical Frailty Scale 4) who was referred to the Geriatrics Clinic from a private neuropsychiatry practice. She lives with her 73-year-old husband in an urban condominium. She demonstrates excellent functional capacity, independently managing complex tasks including her personal finances (via online banking), a complicated medication regimen, and daily smartphone use (she abstains from driving solely due to fear).

Her past medical history is significant for left invasive ductal carcinoma (diagnosed in 2013, currently in remission after WLE, chemoradiotherapy, and five years of Tamoxifen) and cardiometabolic comorbidities (DM, HTN, DLP).

History of Presenting Illness

Mdm PCL has a long-standing history of bipolar mood disorder diagnosed in 2009. Past manic episodes were characterized by grandiosity and impulsivity, including attempting to purchase entire store inventories at KLIA in 2007 (requiring police intervention) and transferring large sums of money online under the delusion of hiring a celebrity for her 60th birthday. For over a decade, she was maintained on sodium valproate, lithium, and risperidone.

In April 2023, she developed hand tremors that severely interfered with feeding, alongside gait instability resulting in several non-injurious falls. Her neuropsychiatrist diagnosed her with Parkinson’s disease, discontinuing lithium and risperidone while up-titrating sodium valproate to 1000 mg daily. Concurrently, levodopa/benserazide and trihexyphenidyl were initiated. Following a suspected mood relapse in December 2023, quetiapine and lorazepam were added.

Subsequently, in 2024, her husband reported intermittent short-term memory lapses (e.g., occasionally forgetting a recent meal, misplacing items, and repetitive questioning). These prompted a diagnosis of dementia and the initiation of memantine, followed by donepezil. However, this reported cognitive decline appears inconsistent with her preserved instrumental activities of daily living (IADLs) and intact executive function.

Current Medications

Neuropsychiatric:

o Sodium Valproate ER 1000 mg OD

o Quetiapine 25 mg ON

o Lorazepam 0.5 mg ON

o Levodopa/Benserazide (Madopar) 125 mg TDS

o Trihexyphenidyl (Artane) 2 mg BD

o Memantine 5 mg OM

o Donepezil 5 mg OM

Cardiometabolic:

o Metformin 1 g BD

o Simvastatin 20 mg ON

Physical and Cognitive Examination

o General: Vitals were stable (BP 120/68, HR 71). Notably, she has a low body weight of 44.8 kg.

o Neurological Motor: Examination revealed an absence of mask-like facies, lead- pipe rigidity, or bradykinesia. She exhibited a prominent postural and kinetic tremor (particularly evident on the finger-to-nose maneuver) that suppressed completely when the limbs were supported at rest. During passive movement, this tremor superimposed on normal muscle tone, creating a false cogwheel-like sensation. Her gait demonstrated a mildly stooped posture with preserved arm swing and no delayed initiation or shuffling. However, she exhibited marked axial instability, prominent en bloc turning, and a propensity for retropulsion.

o Cognitive Mood: Her Montreal Cognitive Assessment (MoCA) score was 18/30, with pronounced deficits in visuospatial/executive function (1/5), attention (3/6), language (1/3), abstraction (1/2), and delayed recall (3/5). Her Geriatric Depression Scale (GDS) was 1/15.

Investigations (12/06/26)

o Therapeutic Drug Monitoring: Serum Valproate 609 µmol/L (Ref: 346-693 µmol/L).

o Hematology: Hb 10.3 g/dL, Platelets 149, Ferritin 23, TSAT 17%.

o Cardiometabolic: HbA1c 5.7%, FBS 3.9 mmol/L, LDL 1.8 mmol/L.

o Reversible Dementia Screen: Vitamin B12 304 pmol/L, Folate 36 nmol/L, TSH 3.02mIU/L, FT4 10.1 pmol/L.

o Renal Hepatic: Normal (Cr 47, Alb 40, AST 26, ALT 3).

o Neuroimaging: A baseline CT Brain is scheduled for 19/08/26.

Questions for Discussion

1. Given her low body weight (44.8 kg), how should we interpret her normal valproate level?

2. What prescribing cascade is evident in this case?

3. What differentiates her presentation from idiopathic Parkinson's disease?

4. What is the most appropriate next step in management, and how would you prioritize the deprescribing process?

We invite members to share their insights on these discussion questions in the comments section below. The formal case resolution will be posted at the end of the month.

Suggested Reading References

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I. Turk Psikiyatri Derg. 2016;27(3):213-217.

2. Rochon PA, Gurwitz JH. The prescribing cascade revisited. Lancet. 2017;389(10081):1778-1780. doi:10.1016/S0140-6736(17)31188-1.

3. Thanvi B, Treadwell S. Drug induced parkinsonism: a common cause of parkinsonism in older people. Postgrad Med J. 2009;85(1004):322-326. doi:10.1136/pgmj.2008.073312

4. Sekiguchi K, Mashiko T, Koide R, et al. A case of long-term exposure to valproic

acid mimicking tremor-dominant parkinson's disease. Tremor Other Hyperkinet Mov (N Y). 2023;13:17. doi:10.5334/tohm.755.

5. Fox C, Richardson K, Maidment ID, et al. Anticholinergic medication use and

cognitive impairment in the older population: the medical research council cognitive function and ageing study. J Am Geriatr Soc. 2011;59(8):1477-1483.

doi:10.1111/j.1532-5415.2011.03491.x.

6. Masmoudi K, Gras-Champel V, Bonnet I, et al. Démence et troubles extra-

pyramidaux sous acide valproïque au long cours [Dementia and extrapyramidal

problems caused by long-term valproic acid]. Therapie. 2000;55(5):629-634.

7. Parsons C, Lim WY, Loy C, et al. Withdrawal or continuation of cholinesterase

inhibitors or memantine or both, in people with dementia. Cochrane Database Syst Rev. 2021;2(2):CD009081. doi:10.1002/14651858.CD009081.pub2.